Lubon H
Plasma Derivatives Department, American Red Cross, Rockville, Maryland, USA.
Biotechnol Annu Rev. 1998;4:1-54. doi: 10.1016/s1387-2656(08)70066-8.
The regulatory elements of genes used to target the tissue-specific expression of heterologous human proteins have been studied in vitro and in transgenic mice. Hybrid genes exhibiting the desired performance have been introduced into large animals. Complex proteins like protein C, factor IX, factor VIII, fibrinogen and hemoglobin, in addition to simpler proteins like alpha 1-antitrypsin, antithrombin III, albumin and tissue plasminogen activator have been produced in transgenic livestock. The amount of functional protein secreted when the transgene is expressed at high levels may be limited by the required posttranslational modifications in host tissues. This can be overcome by engineering the transgenic bioreactor to express the appropriate modifying enzymes. Genetically engineered livestock are thus rapidly becoming a choice for the production of recombinant human blood proteins.
用于靶向异源人类蛋白质组织特异性表达的基因调控元件已在体外和转基因小鼠中进行了研究。表现出所需性能的杂交基因已被引入大型动物体内。除了α1-抗胰蛋白酶、抗凝血酶III、白蛋白和组织纤溶酶原激活剂等较简单的蛋白质外，蛋白质C、因子IX、因子VIII、纤维蛋白原和血红蛋白等复杂蛋白质也已在转基因家畜中产生。当转基因高水平表达时，分泌的功能蛋白量可能会受到宿主组织中所需翻译后修饰的限制。这可以通过改造转基因生物反应器以表达适当的修饰酶来克服。因此，基因工程家畜正迅速成为生产重组人血蛋白的一种选择。
